Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5

Margaret J. McMillin, Anita E. Beck, Jessica X. Chong, Kathryn M. Shively, Kati J. Buckingham, Heidi I S Gildersleeve, Mariana I. Aracena, Arthur S. Aylsworth, Pierre Bitoun, John C. Carey, Carol L. Clericuzio, Yanick J. Crow, Cynthia J. Curry, Koenraad Devriendt, David B. Everman, Alan Fryer, Kate Gibson, Maria Luisa Giovannucci Uzielli, John M. Graham, Judith G. Hall & 25 others Jacqueline T. Hecht, Randall A. Heidenreich, Jane A. Hurst, Sarosh Irani, Ingrid P C Krapels, Jules G. Leroy, David Mowat, Gordon T. Plant, Stephen P. Robertson, Elizabeth K. Schorry, Richard H. Scott, Laurie H. Seaver, Elliott Sherr, Miranda Splitt, Helen Stewart, Constance Stumpel, Sehime G. Temel, David Weaver, Margo Whiteford, Marc S. Williams, Holly K. Tabor, Joshua D. Smith, Jay Shendure, Deborah A. Nickerson, Michael J. Bamshad

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.

Original languageEnglish
Pages (from-to)734-744
Number of pages11
JournalAmerican Journal of Human Genetics
Volume94
Issue number5
DOIs
StatePublished - May 1 2014

Fingerprint

Mutation
Cleft Palate
Exome
Molecular Probes
Contracture
Ion Channels
Foot
Hand
Marden-Walker syndrome
Gordon syndrome
Oculomelic amyoplasia
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

McMillin, M. J., Beck, A. E., Chong, J. X., Shively, K. M., Buckingham, K. J., Gildersleeve, H. I. S., ... Bamshad, M. J. (2014). Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5. American Journal of Human Genetics, 94(5), 734-744. https://doi.org/10.1016/j.ajhg.2014.03.015

Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5. / McMillin, Margaret J.; Beck, Anita E.; Chong, Jessica X.; Shively, Kathryn M.; Buckingham, Kati J.; Gildersleeve, Heidi I S; Aracena, Mariana I.; Aylsworth, Arthur S.; Bitoun, Pierre; Carey, John C.; Clericuzio, Carol L.; Crow, Yanick J.; Curry, Cynthia J.; Devriendt, Koenraad; Everman, David B.; Fryer, Alan; Gibson, Kate; Giovannucci Uzielli, Maria Luisa; Graham, John M.; Hall, Judith G.; Hecht, Jacqueline T.; Heidenreich, Randall A.; Hurst, Jane A.; Irani, Sarosh; Krapels, Ingrid P C; Leroy, Jules G.; Mowat, David; Plant, Gordon T.; Robertson, Stephen P.; Schorry, Elizabeth K.; Scott, Richard H.; Seaver, Laurie H.; Sherr, Elliott; Splitt, Miranda; Stewart, Helen; Stumpel, Constance; Temel, Sehime G.; Weaver, David; Whiteford, Margo; Williams, Marc S.; Tabor, Holly K.; Smith, Joshua D.; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.

In: American Journal of Human Genetics, Vol. 94, No. 5, 01.05.2014, p. 734-744.

Research output: Contribution to journalArticle

McMillin, MJ, Beck, AE, Chong, JX, Shively, KM, Buckingham, KJ, Gildersleeve, HIS, Aracena, MI, Aylsworth, AS, Bitoun, P, Carey, JC, Clericuzio, CL, Crow, YJ, Curry, CJ, Devriendt, K, Everman, DB, Fryer, A, Gibson, K, Giovannucci Uzielli, ML, Graham, JM, Hall, JG, Hecht, JT, Heidenreich, RA, Hurst, JA, Irani, S, Krapels, IPC, Leroy, JG, Mowat, D, Plant, GT, Robertson, SP, Schorry, EK, Scott, RH, Seaver, LH, Sherr, E, Splitt, M, Stewart, H, Stumpel, C, Temel, SG, Weaver, D, Whiteford, M, Williams, MS, Tabor, HK, Smith, JD, Shendure, J, Nickerson, DA & Bamshad, MJ 2014, 'Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5', American Journal of Human Genetics, vol. 94, no. 5, pp. 734-744. https://doi.org/10.1016/j.ajhg.2014.03.015
McMillin, Margaret J. ; Beck, Anita E. ; Chong, Jessica X. ; Shively, Kathryn M. ; Buckingham, Kati J. ; Gildersleeve, Heidi I S ; Aracena, Mariana I. ; Aylsworth, Arthur S. ; Bitoun, Pierre ; Carey, John C. ; Clericuzio, Carol L. ; Crow, Yanick J. ; Curry, Cynthia J. ; Devriendt, Koenraad ; Everman, David B. ; Fryer, Alan ; Gibson, Kate ; Giovannucci Uzielli, Maria Luisa ; Graham, John M. ; Hall, Judith G. ; Hecht, Jacqueline T. ; Heidenreich, Randall A. ; Hurst, Jane A. ; Irani, Sarosh ; Krapels, Ingrid P C ; Leroy, Jules G. ; Mowat, David ; Plant, Gordon T. ; Robertson, Stephen P. ; Schorry, Elizabeth K. ; Scott, Richard H. ; Seaver, Laurie H. ; Sherr, Elliott ; Splitt, Miranda ; Stewart, Helen ; Stumpel, Constance ; Temel, Sehime G. ; Weaver, David ; Whiteford, Margo ; Williams, Marc S. ; Tabor, Holly K. ; Smith, Joshua D. ; Shendure, Jay ; Nickerson, Deborah A. ; Bamshad, Michael J. / Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5. In: American Journal of Human Genetics. 2014 ; Vol. 94, No. 5. pp. 734-744.
@article{c5e88bd0c6c74c5fa42c0abb280435d7,
title = "Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5",
abstract = "Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83{\%}] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82{\%}) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.",
author = "McMillin, {Margaret J.} and Beck, {Anita E.} and Chong, {Jessica X.} and Shively, {Kathryn M.} and Buckingham, {Kati J.} and Gildersleeve, {Heidi I S} and Aracena, {Mariana I.} and Aylsworth, {Arthur S.} and Pierre Bitoun and Carey, {John C.} and Clericuzio, {Carol L.} and Crow, {Yanick J.} and Curry, {Cynthia J.} and Koenraad Devriendt and Everman, {David B.} and Alan Fryer and Kate Gibson and {Giovannucci Uzielli}, {Maria Luisa} and Graham, {John M.} and Hall, {Judith G.} and Hecht, {Jacqueline T.} and Heidenreich, {Randall A.} and Hurst, {Jane A.} and Sarosh Irani and Krapels, {Ingrid P C} and Leroy, {Jules G.} and David Mowat and Plant, {Gordon T.} and Robertson, {Stephen P.} and Schorry, {Elizabeth K.} and Scott, {Richard H.} and Seaver, {Laurie H.} and Elliott Sherr and Miranda Splitt and Helen Stewart and Constance Stumpel and Temel, {Sehime G.} and David Weaver and Margo Whiteford and Williams, {Marc S.} and Tabor, {Holly K.} and Smith, {Joshua D.} and Jay Shendure and Nickerson, {Deborah A.} and Bamshad, {Michael J.}",
year = "2014",
month = "5",
day = "1",
doi = "10.1016/j.ajhg.2014.03.015",
language = "English",
volume = "94",
pages = "734--744",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5

AU - McMillin, Margaret J.

AU - Beck, Anita E.

AU - Chong, Jessica X.

AU - Shively, Kathryn M.

AU - Buckingham, Kati J.

AU - Gildersleeve, Heidi I S

AU - Aracena, Mariana I.

AU - Aylsworth, Arthur S.

AU - Bitoun, Pierre

AU - Carey, John C.

AU - Clericuzio, Carol L.

AU - Crow, Yanick J.

AU - Curry, Cynthia J.

AU - Devriendt, Koenraad

AU - Everman, David B.

AU - Fryer, Alan

AU - Gibson, Kate

AU - Giovannucci Uzielli, Maria Luisa

AU - Graham, John M.

AU - Hall, Judith G.

AU - Hecht, Jacqueline T.

AU - Heidenreich, Randall A.

AU - Hurst, Jane A.

AU - Irani, Sarosh

AU - Krapels, Ingrid P C

AU - Leroy, Jules G.

AU - Mowat, David

AU - Plant, Gordon T.

AU - Robertson, Stephen P.

AU - Schorry, Elizabeth K.

AU - Scott, Richard H.

AU - Seaver, Laurie H.

AU - Sherr, Elliott

AU - Splitt, Miranda

AU - Stewart, Helen

AU - Stumpel, Constance

AU - Temel, Sehime G.

AU - Weaver, David

AU - Whiteford, Margo

AU - Williams, Marc S.

AU - Tabor, Holly K.

AU - Smith, Joshua D.

AU - Shendure, Jay

AU - Nickerson, Deborah A.

AU - Bamshad, Michael J.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.

AB - Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.

UR - http://www.scopus.com/inward/record.url?scp=84899963553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899963553&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2014.03.015

DO - 10.1016/j.ajhg.2014.03.015

M3 - Article

VL - 94

SP - 734

EP - 744

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -